Pfizer’s Paxlovid study does not answer key questions about benefits for broader populations

PFizer said Tuesday that a widely publicized study of its antiviral Paxlovid in patients who have Covid but do not have risk factors for serious illness showed no benefit in speeding up the relief of Covid symptoms but preventing doctor visits and hospitalizations seemed.

In addition, due to the overall low number of hospitalizations in the study, no statistically significant finding could be made as to whether patients who had previously been vaccinated against Covid were hospitalized less often when they received Paxlovid.

The data in no way invalidates previous findings showing Paxlovid prevents hospital admissions and saves lives in patients at high risk for severe Covid. But the results, published in a press release, are likely to take time for experts to digest and understand.

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“I think it has to be said that it’s difficult to draw any conclusions based on a press release, but these data seem intriguing but unconvincing,” said Andy Pavia, head of the Department of Pediatric Infectious Diseases at the University of Utah Hospital.

The results are likely to spark debate about how cautious doctors should be when prescribing Paxlovid. Pfizer’s profound early results came from a group of unvaccinated, high-risk patients. But the Food and Drug Administration has approved it for anyone with at least one risk factor, such as diabetes or high blood pressure; Anecdotally, doctors report that the drug is being used extensively in high-risk vaccinated patients, especially given a major push by the US government to ensure the drug reaches all those indicated to receive it.

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Still, there was little data on how well the drug worked in these high-risk vaccinated patients, and there were open questions about whether it might also be useful in patients without risk factors.

“This reinforces that Paxlovid will not play a major role in vaccinated people, except in people who may be most at risk,” said Walid Gellad, director of the Center for Pharmaceutical Policy and Prescribing at the University of Pittsburgh. “Maybe it would be statistically significant in a larger study, but the effect is small.”

In a statement, Pfizer CEO Albert Bourla said: “With it being estimated that up to 40-50% of people around the world are at high risk, we believe there remains a significant unmet need for treatment options to combat this disease , and we will continue to prioritize efforts to advance the development of Paxlovid.”

However, Gellad argued that the data suggest that finding the subset of patients at highest risk is crucial, especially given the drug’s associated side effects and low potential for relapse.

“We really need to understand who is really at high risk and we need to know who is going to be hospitalized,” he said.

Real-world studies in largely — but not fully — vaccinated populations in Hong Kong and Israel have also indicated that Paxlovid may offer some benefit to lower-risk patients, with a recent Israeli study finding that the drug increased the risk of serious illness or death in patients reduced by 46% covered by the largest local healthcare provider.

The Israeli study suggested that the drug has the greatest benefit for patients with a neurological condition, a malignant condition, or those on immunosuppressive drugs.

Real studies in largely – but not fully – vaccinated populations in Hong Kong and Israel have also indicated that Paxlovid may offer some benefit to lower-risk patients, according to the largest local healthcare provider.

The Israeli study suggested that the drug has the greatest benefit for patients with a neurological condition, a malignant condition, or those on immunosuppressive drugs.

Pfizer said in December that an early look at the study was unlikely to achieve its primary goal of showing relief from Covid symptoms after four days, but that patients who received Paxlovid appeared less likely to need medical care than those who received who received placebo.

In an updated analysis of 1,153 patients enrolled in the study through December 2021, there was a 51% difference in medical care needs – that’s five patients who needed them in the treatment arm compared to 10 on placebo – but that Result it was not statistically significant.

However, the results were similar in patients who had previously been vaccinated. Originally, the study included volunteers who were fully vaccinated but at high risk for Covid symptoms. After Paxlovid was approved for these people, they could no longer be included in the study. Pfizer changed entry criteria to include people whose last vaccination was at least 12 months prior to enrollment.

A subgroup analysis of 721 vaccinated adults with at least one risk factor for progression to severe Covid showed that patients who received Paxlovid were 57% less likely to be hospitalized or die, but the result was not statistical significant. There were three patients who were hospitalized or died in the Paxlovid group, compared with seven in the placebo group.

Davey Smith, an infectious disease expert at the University of California, San Diego, said he considers the data supportive of giving Paxlovid to those who have been vaccinated and have contracted Covid and who have at least one high risk factor.

“It answers a question that has been open for some time: whether or not vaccinated people with high-risk diseases should be treated. I and other doctors have done this. But it’s good to have some certainty.”

Even without statistical significance, he said, “I think everything points in the right direction.”

Pavia said that a big question about whether people at lower risk should receive Paxlovid will not be the study results, but whether or not strains of the SARS-CoV-2 virus will develop resistance to the drug as it becomes more widespread. If little resistance develops, doctors can use the drug extensively. But if there’s a risk of resistance, they’ll likely keep it in reserve for higher-risk patients.

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